The new Comprehensive Sickle Cell Center at Johns Hopkins University and University of Alabama (JHU/UAB CSCC) will represent a collaboration between two institutions with strong records of research, patient services and clinical care for patients with sickle cell disease (SCD). The center will have 3 goals: 1) through separate but complementary Clinical Cores at both JHU and UAB, to provide state-of-the-art comprehensive care for adult and pediatric SCD patients at their respective institutions, plus infrastructure to carry out inter-Center collaborative and intra-Center translational research at both institutions;2) through our Patient Services Core, to provide high quality and improved patient services by evaluating, coordinating, and expanding diagnostic, educational, counseling and legal services for children and adults with SCD and their families, 3) through our Research Projects, to carry out and stimulate new SCD-related basic science and clinical research within both universities and increase collaborations between JHU, UAB, and other Centers. An Administrative Core based at JHU will coordinate and implement local and collaborative CSCC activities. Four research projects are proposed. Our inter-Center trial, will assess the usefulness of hydroxyurea therapy for patients with conditional transcranial Doppler measurements. This trial has the potential to prevent the need for transfusions and provide primary prevention for stroke in a large percentage of patients with SCD at risk for this common and devastating complication. Our Patient Services Project will explore the effect of local public health services on mortality outcomes for SCD. Through this project, we will identify the critical public health interventions of high impact that may account for the marked state-to-state variability in SCD mortality. Our Basic Science Project will take advantage of unique resources (the SIT Trail Biologic Repository and JHU Center for Proteomics) to study potential biomarkers for silent cerebral infarction, a leading cause of neurologic morbidity in SCD. Our Translational Project will exploit ongoing basic research observations on the role of NO and oxidative damage in priapism, to inform a clinical trial that will assess the effect of sildenafil, a modulator of NO function in vivo, for the treatment of priapism in SCD. Our center will take advantage of the rich basic science and clinical research resources in the combined JHU/UAB environment to improve care, services and quality of life for SCD patients locally and nationally.